In this study, we explored the association of MGP and NOS3 polymorphisms with the susceptibility of CKD and its associated cardiovascular comorbidity in South Indian Tamils, and our data showed that TT and CT genotypes of NOS3 (rs2070744) and TTA and CCG haplotypes of MGP (1-rs4236; 2-rs1800801; 3-rs1800802) genetic variants are associated with CKD risk in South Indian Tamils. The gene discussed is NOS3; the disease is chronic kidney disease.